We examined the presence of human papillomavirus (HPV) DNA sequences in tissues of verrucous carcinoma (VC) of the lip. Detection and typing of HPV DNA was performed using polymerase chain reaction with sequence analysis and restriction fragment length polymorphism analysis. All tissues of VC contained HPV DNA and one of recurrent case was infected with four different HPV DNAs including high risk types. Seven different HPV types were detected in VC, of which (accession no. in EMBL/GeneBank/DDBJ databases) has been described as a partial sequences from an unknown HPV type. Sequence analysis showed that HPVX is related to HPV-20 (74.8% sequence homology). These results indicate that various mucosal and cutaneous HPVs of high risk types are associated with the one of pathogenesis of VC of the lip. In addition, the relationship between VC of the lip and HPV infection is discussed, as is therapy against VC.